h151  (MedChemExpress)

Journal: Eye and Vision

Article Title: STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice

doi: 10.1186/s40662-026-00475-3

Figure Lengend Snippet: In vivo effects of the STING inhibitor H151 on proliferation after glaucoma filtration surgery (GFS). a Representative images from the Sham, GFS, and GFS + H151 groups. Yellow circles indicate the blebs. b Bleb survival analysis of the GFS and GFS + H151 groups using Kaplan–Meier survival curves (n = 5 eyes in each group). c Histological analysis of ocular tissues by hematoxylin and eosin (H&E) staining from the Sham, GFS, and GFS + H151 groups (n = 3 eyes in each group). The triangles indicate the conjunctiva, the stars indicate the retina. d Immunofluorescence staining of α-SMA to evaluate myofibroblast activation in the Sham, GFS, and GFS + H151 groups (n = 3 eyes in each group). The triangles indicate the conjunctiva. e Masson stained tissue sections from the Sham, GFS, and GFS + H151 groups. The triangles indicate the conjunctiva, the stars indicate the retina. f Sirius red staining of tissue sections from the Sham, GFS, and GFS + H151 groups. The triangles indicate the conjunctiva, the stars indicate the retina. g Analysis of Masson staining (n = 3 eyes in each group). h Analysis of Sirius red staining (n = 3 eyes in each group). i Double immunofluorescence staining of STING (red), F4/80 (green), and DAPI (blue) in the Sham, GFS, and GFS + H151 groups (n = 3 eyes in each group). The triangles indicate the conjunctiva, the stars indicate the retina. Arrows indicate the co-localization of STING and F4/80 in the GFS group. j Immunofluorescence staining of p-p65 to assess NF-κB activation in the Sham, GFS, and GFS + H151 groups (n = 3 eyes in each group). The triangles indicate the conjunctiva, the stars indicate the retina. Arrows indicate the p-p65 expression area. k Relative mRNA expression of TNF-α, IL-18, IL-6, and IL-1β in the Sham, GFS, and GFS + H151 groups (n = 5 eyes in each group). l Relative mRNA expression of fibronectin, CTGF, COL1A1, α-SMA, and COL3A1 in the Sham, GFS, and GFS + H151 groups (n = 5 eyes in each group). Results were expressed as mean ± SD. Statistical analysis was performed using log-rank test ( b ) and one-way ANOVA followed by Bonferroni’s post-hoc test ( g , h , k , l ). #, Welch’s ANOVA with Dunnett's T3 post-hoc test. * P < 0.05, ** P < 0.01, *** P < 0.001. STING, stimulator of interferon genes; H151, STING inhibitor; Sham, sham-operated; α-SMA, α-smooth muscle actin; F4/80, macrophage marker; DAPI, 4′,6-diamidino-2-phenylindole; p-p65, phospho-p65; NF-κB, nuclear factor kappa-B; TNF-α, tumor necrosis factor-α; IL, interleukin; CTGF, connective tissue growth factor; COL1A1, collagen type I alpha 1; COL3A1, collagen type III alpha 1

Article Snippet: H151 (HY-112693) and SB203580 (HY-10256) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: In Vivo, Filtration, Staining, Immunofluorescence, Activation Assay, Double Immunofluorescence Staining, Expressing, Marker

Journal: Eye and Vision

Article Title: STING deficiency alleviates scar formation after glaucoma filtration surgery by suppressing p38 MAPK-induced inflammation in mice

doi: 10.1186/s40662-026-00475-3

Figure Lengend Snippet: In vitro effects of H151 on inflammation and fibrosis of Ang II-induced HTFs. a Immunofluorescence staining of HTFs to identify α-SMA after the treatment with Ang II and Ang II + H151 (n = 3 eyes in each group). b , c Wound healing assay: cells were incubated with or without H151 2 h before Ang II (1 μM) treatment for 24 h. Subsequently, the wound scratches were imaged and quantified (n = 3 eyes in each group). b Representative images of the different treatment groups at different time points after the scratch. c Relative migration rates in each group. d Relative mRNA expression of TNF-α, IL-18, IL-6, and IL-1β in control, Ang II, and Ang II + H151 groups (n = 3 eyes in each group). e Relative mRNA expression of fibronectin, CTGF, COL1A1, α-SMA, and COL3A1 in control, Ang II, and Ang II + H151 groups (n = 3 eyes in each group). f , g Representative immunoblotting images: H151 significantly inhibited Ang II-induced p-p38, α-SMA, and collagen I protein expression by western blot (n = 3 eyes in each group). Results were expressed as mean ± SD. Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post-hoc test ( d , e , g ) and two-way ANOVA followed by Bonferroni’s post-hoc test ( c ). ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001. H151, STING inhibitor; Ang II, angiotensin II; HTFs, human Tenon’s capsule fibroblasts; α-SMA, α-smooth muscle actin; TNF-α, tumor necrosis factor-α; IL, interleukin; CTGF, connective tissue growth factor; COL1A1, collagen type I alpha 1; COL3A1, collagen type III alpha 1; p-p38, phospho-p38; DAPI, 4′,6-diamidino-2-phenylindole

Article Snippet: H151 (HY-112693) and SB203580 (HY-10256) were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: In Vitro, Immunofluorescence, Staining, Wound Healing Assay, Incubation, Migration, Expressing, Control, Western Blot

Journal: bioRxiv

Article Title: Myeloid PINK1 represses mtDNA release and immune signaling that impacts neuronal pathology in patient-derived idiopathic PD models

doi: 10.64898/2026.01.07.694713

Figure Lengend Snippet: A) Graphical representation of methodology and findings adapted from Gulen et al. to identify genes induced by the innate immune pathway involving STING, herein referred to as STING-responsive genes (SRG). Cells taken from either skin of human healthy donors, which are then irradiated to promote aging, or brains from old mice were treated with STING inhibitor (H-151). RNAseq (validated by qPCR) was then performed to interrogate the expression of inflammatory genes induced through the activation of the STING pathway during aging. Using their combined data, a list of SRG comprising of 108 genes was compiled (full list shown in Supp. Table 2). B) Dot plot indicating the average expression of SRG across all conditions from the single-cell RNAseq dataset of human iPSC-derived peripheral myeloid cells wherein a larger view showcases key proinflammatory cytokines/chemokines and type I interferons within the SRG panel. The size of the dot determines the proportion of cells expressing the particular gene/gene set while the color scale dictates the normalized average expression. C) Representative immunofluorescence staining of macrophages from human (hiPSC-MDM) and mouse (BMDM) origins for DNA (red) and mitochondria (green) using anti-DNA antibody and AlexaFluor 647-labelled MitoTracker or anti-TOMM40 antibody, respectively. Scale bars: 10 μm and 2 μm (inset). The red-positive puncta dissociated from the mitochondria (green signal) was defined as cytosolic DNA in WT and PiKO stimulated cells, as well as non-stimulated controls. Open and closed squares represent data point for human and mouse experiments, respectively. Two-way ANOVA followed by Holm-Sidak’s multiple comparison test was applied. Mean ± SEM, n=5 independent experiment with each experiment comprised of 20-25 images analyzed. D, E) Representative immunoblots of human and mouse macrophages stained with anti-STING and anti-phospho NF-κβ (pNF-κβ) antibodies. β-actin was used as loading control. The relative protein expression of STING and pNF-κβ in WT and PiKO stimulated cells, as well as non-stimulated controls, were quantified and normalized to β-actin. Open and closed squares represent data point for human and mouse experiments, respectively. Two-way ANOVA followed by Tukey’s multiple comparison test was applied. Mean ± SEM, n=5 independent experiments.

Article Snippet: Matured macrophages were replated and co-stimulated with 500 ng/mL Ultrapure lipopolysaccharide (LPS) from E.coli O111:B4 (Invivogen, tlrl-3pelps) and 50 ng/mL mouse recombinant interleukin-1beta (IL-1β) (PeproTech, 211-11B) with or without 8 μg/mL small molecule STING antagonist H-151 (InvivoGen, inh-h151) for 6 h. For the exchange medium experiment, bone marrow-derived macrophages (BMDM) were treated with inflammatory stimuli for 24 h then cells were washed, and conditioned medium (CM) was collected 24 h later.

Techniques: Irradiation, Expressing, Activation Assay, Derivative Assay, Immunofluorescence, Staining, Comparison, Western Blot, Control

Journal: bioRxiv

Article Title: Myeloid PINK1 represses mtDNA release and immune signaling that impacts neuronal pathology in patient-derived idiopathic PD models

doi: 10.64898/2026.01.07.694713

Figure Lengend Snippet: A) Graphical representation of mtDNA-dependent STING/NF-κβ signaling pathway resulting in inflammation, underscoring H-151 as a STING inhibitor. B) Schematic diagram to describe cell fractionation using commercially available buffers and differential centrifugation. Shown are representative immunoblots of cytosolic (cyto) and mitochondrial (mito) fractions isolated from stimulated WT and PiKO BMDM indicating purity of subcellular fractions according to the expression of mitochondrial protein TOMM20 and cytosolic protein GAPDH. β-actin was used as loading control. Both fractions from stimulated BMDM of WT and PiKO mice were assessed for relative gene expression of mtDNA (MT-ND1). Relative ratios of cyto-to-mito MT-ND1 (cyto/mito) in stimulated PiKO with and without H-151 were normalized to corresponding WT groups. Two-way ANOVA followed by Tukey’s multiple comparison test was applied. Mean ± SEM, n=3 mice per group. C) Representative immunoblots of WT and PiKO BMDM stained with anti-pNF-κβ and anti-STING antibodies. β-actin was used as loading control. The relative protein expression of pNF-κβ and STING in stimulated cells with or without H-151, as well as non-stimulated controls, were quantified and normalized to β-actin. Two-way ANOVA followed by Tukey’s multiple comparison test was applied. Mean ± SEM, n=4 mice per group. D) Quantification of inflammatory target genes downstream of STING innate immune pathway (IL6 and IFNB1) by qPCR across all conditions. Twoway ANOVA followed by Tukey’s multiple comparison test was applied. Mean ± SEM, n=6-7 mice per group.

Article Snippet: Matured macrophages were replated and co-stimulated with 500 ng/mL Ultrapure lipopolysaccharide (LPS) from E.coli O111:B4 (Invivogen, tlrl-3pelps) and 50 ng/mL mouse recombinant interleukin-1beta (IL-1β) (PeproTech, 211-11B) with or without 8 μg/mL small molecule STING antagonist H-151 (InvivoGen, inh-h151) for 6 h. For the exchange medium experiment, bone marrow-derived macrophages (BMDM) were treated with inflammatory stimuli for 24 h then cells were washed, and conditioned medium (CM) was collected 24 h later.

Techniques: Cell Fractionation, Centrifugation, Western Blot, Isolation, Expressing, Control, Gene Expression, Comparison, Staining